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CLINICAL VIGNETTE 2017; 3:1

MANAGEMENT OF NON-FUNCTIONING PITUITARY TUMOURS

Editor-in-Chief: Olufemi E. Idowu. Neurological surgery Division, Department of Surgery, LASUCOM/LASUTH, Ikeja, Lagos, Nigeria.

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MANAGEMENT OF NON-FUNCTIONING PITUITARY TUMOURS

DR JULIUS M. VITOWANU

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

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CASE PRESENTATION • NAME: M.R.

• AGE: 62 years • GENDER: Male

• OCCUPATION: Fashion designer • PC:

Bilateral visual impairment x2years

Headache x2years

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CLINICAL EVALUATION HISTORY • Difficulty with vision (loss of peripheral vision) started with the left eye, progressed to the right 6 months later • Headache was around the vertex, dull, persistent, aggravated by sneezing, coughing, and straining; wakes him at night EXAMINATION

• Conscious ,not pale ,anicteric ,acyanosed, nil pedal oedema • Pupils 3.5mm in size bilaterally, reactive to light • Right eye– no light perception, Left eye- light perception

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INVESTIGATIONS • Assessment: Sellar/suprasellar mass with optic chiasma compression • Pituitary function Test: low LH and Testosterone. – LH – 0.65µIU/ml (1.8-2.0) – testosterone <1.0ng/ml

SURGERY • Right pterional craniotomy with sellar tumor excision • Intra-operative findings ; – stretched , splayed , bowed right optic nerve – Firm haemorrhagic sellar/suprasellar tumour Copyright- Frontiers of Ikeja Surgery, 2017; 3:1

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POST-OPERATIVE • Discharged to clinic, 2 weeks after surgery • Follow up visit 2 weeks after discharge – Visual Deficit remains, headaches resolved

• Post-operative Pituitary function test – Low cortisol – 3.1µg/dl (5- 23) – Low TSH – 0.069µIU/ml (0.3 – 4.2) – Low T4 - <20µIU/ml

• Post-operative Treatment – Levothyroxine 100ug daily – Tabs hydrocotisone 10mg daily Copyright- Frontiers of Ikeja Surgery, 2017; 3:1

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PITUITARY ANATOMY  Comprises anatomically and functionally distinct  Anterior pituitary lobe (adenohypophysis)  Posterior pituitary lobe (Neurohypophysis)  Entirely ectodermal in origin  Adenohypophysis  Develops from Rathke’s pouch  Upward invagination  Neurohypophysis  Develops from the infundibulum  Downward extension of the floor of the diencephalon

 Occupies a cavity of the sphenoid bone called sella turcica  Roof is formed by diaphragm sellae  The stalk of pituitary is attached above to the floor of third ventricle  Measures about 15 mm in antpost and 12 mm in supero inferior axis  Weighs- 0.5 gm

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NON-FUNCTIONING PITUITARY TUMOURS (NFPA) • Tumours of the pituitary gland that are characterized by the absence of clinical and biochemical evidence of pituitary hormonal overproduction • Constitute 25 – 30 % of pituitary tumours • Usually histologically benign • Symptoms are usually due to size and pressure effects on the surrounding structures – velocity and direction of tumour growth

Folate receptor α (FRα), a high-affinity folate transporter, is significantly overexpressed in clinically nonfunctional adenomas but not in functional adenomas

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AETIOPATHOGENESIS • Monoclonal in origin ,due to genetic mutations in a single cell • Precise mechanisms yet to be understood Oncogenes • c-myc oncogene • stimulatory guanine nucleotide-binding protein (gsp) gene • pituitary tumor transforming gene (PTTG • Cyclin D1 (CCND1) • H-ras oncogene) Copyright- Frontiers of Ikeja Surgery, 2017; 3:1

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CLINICAL PRESENTATION • Asymptomatic- Incidentalomas are mostly microadenomas (about 2/3), confined to the sella turcica and usually do not cause any signs or symptoms • Symptomatic-Due to pressure effect of enlarging pituitary mass in the cranial cavity – Headaches – Vomiting – Visual defect: Bitemporal field defects are the most common, Impaired visual acuity, abnormal pupillary light reaction, color vision can be affected, ophthalmoplegia, diplopia, ptosis – Hypopituitarism - from mass compression of normal gland, or secretion of inactive hormonal subunits – Galactorrhea – pituitary stalk effect – Pituitary apoplexy- due to acute hemorrhage or infarction of a pituitary gland, Can be lethal

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DIFFERENTIAL DIAGNOSIS • • • • • • • • •

Craniopharyngiomas Meningiomas Neurofibromas Ectopic germinomas Metastatic tumors. Sarcoid Tuberculomas Carotid artery aneurysm Sphenoid sinus mucocele Copyright- Frontiers of Ikeja Surgery, 2017; 3:1

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NEUROIMAGING • MRI – Gold standard – Intrasellar mass – isointense on T1 –weighted , different enhancement patterns post contrast • • • •

Size Degenerative changes Extra sella extension Consistency

• CT scan – Provides details of bone anatomy – diagnostic imaging study of choice in patients who are unable to undergo an MR study. – Useful in preoperative planning • for the definition of the best route from the nasal cavity toward the sellar

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EVALUATION • Imaging – Identify the lesion – Define spatial situation of the lesion (presurgical planning) – Verify removal of the lesion (postsurgical follow-up)

• Assessment of pituitary function • Ophthalmological assessment – visual field perimetry; visual field defect – Visual Evoke Potential ; latency delay , amplitude reduction

• Histopathological analysis of surgical specimen – Confirm diagnosis – Immunohistochemistry- primary hormones, Ki-67, P53

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TREATMENT    

Non-operative- watchful waiting Surgery Radiotherapy Medical therapy

SURGERY General indication • Pituitary apoplexy • Progressive mass effect - Visual deficits or cranial nerve palsy. Goals • Normalization of excess of hormone secretion, if any • Preservation or even restoration of normal pituitary function • Elimination of mass effect • Preservation or restoration of visual acuity and/or visual field • Prevention of tumor recurrence • Achievement of a complete pathologic diagnosis Copyright- Frontiers of Ikeja Surgery, 2017; 3:1

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SURGERY Surgical Approaches for Pituitary Tumors 1. Trans-Sphenoidal Approach • Microscopic – Sublabial – Trans-septal – Endonasal

• Endoscopic • Combined or endoscope-assisted microsurgery 2. Transcranial Approach • Pterional or frontolateral • Subfrontal unilateral • Subfrontal bilateral interhemispheric • Supraorbital craniotomy • Radical combine approach – recurrence

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SURGERY Indications for transcranial approach • Doubt about diagnosis • Failed transphenoidal surgery – Intrinsic tumour characteristics – Failure of suprasella extension to descend – Falure to remove adequate amount of tumour

• • • •

Para/extrasella extension Coexistence aneurysms Ectactic carotid artery Severe sinus infection

Complications • • • •

• • • • •

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Frontal lobe damage Frontal lobe cyst Anosmia Perioperative optic nerve damage Vascular injuries Hypothalamic damage CSF leakage Electrolyte abnormalities Post op visual deterioration

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RADIOTHERAPY • Mainly used as complementary to surgery – tumors not completely resected by surgery – for patients who, at diagnosis, already present aggressive tumors – tumors with pathologic characteristics that demonstrate aggressiveness

• Primary therapy – patients with tumors proximate or reaching the optic pathway and concurrently present high surgical risk or surgery refusal

• Conventional – in fractionated doses four to five times a week for four weeks

• Stereotactic – Fractionated – Radiosurgery • Gamma knife • Cyber knife

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MEDICAL TREATMENT • Well tolerated and safe molecules, able to reduce tumour size in some instances • Somatostatin analogues • Dopamin agonists – particularly tumours that express long isoforms of D2 receptor • The expression of D2 short rather than D2 long isoform was found to be associated with the most favourable response of the tumor to cabergoline treatment Pivonello et al. • Other drugs – Temozolomide

WATCHFUL WAITING • Employed in carefully selected patients • Regular assessment of pituitary function, MRI and visual field is required.

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FOLLOW UP • Imaging – Imaging exam of the sellar region, preferably MRI, at least 3 months after surgery – Annual MRI in the first 5 years – Every 2-3 years thereafter

• Pituitary function test – Evaluation of pituitary function 1-3 months after the procedure – Then every 6-12 months

• Ophthalmological assessment – Evaluation of the visual field through visual perimetry one month after surgery – Then Annual visual field perimetry

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REFERENCES • • • • •

John A. Jane Jr. et al. Pituitary tumours. Functioning and Nonfunctioning. Youmans neurological surgery 16th edition ch 34 pp 1476 -1509 Pablo S Recinos ,C Rorry Goodwin et al ;SCHMIDEK & SWEET OPERATIVE NEUROSURGICAL TECHNIQUES: transcranial surgery for pituitary macroadenomas Ch 23 pp 280- 91 Maria Licia, Calado de Aguiar, Ribeiro Cury; Non-functioning pituitary adenomas: clinical feature, laboratorial and imaging assessment, therapeutic management and outcome. Clin Endocrinol. Mônica R. Gadelha. Rua Prof. Rodolpho Paulo Rocco,Arch Endocrinol Metab. 2016;60(4):374-90 Soto-Ares G, Cortet-Rudelli C, Assaker R, Boulinguez A, Dubest C, Dewailly D, et al. MRI protocol technique in the optimal therapeutic strategy of non-functioning pituitary adenomas. Eur J Endocrinol. 2002;146(2):179-86 Park P, Chandler WF, Barkan AL, Orrego JJ, Cowan JA, Griffith KA, et al. The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas. Neurosurgery. 2004;55(1):100-6; discussion 67. C. A. Jaffe, “Clinically non-functioning pituitary adenoma,” Pituitary, vol. 9, no. 4, pp. 317–321, 2006. View at Publisher Pivonello R, Matrone C, Filippella M, Cavallo LM, Di Somma C, Cappabianca P, Colao A, Annunziato L & Lombardi G. Dopamine receptor expression and function in clinically non-functioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. Journal of Clinical Endocrinology and Metabolism 2004 89 1674–1683

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Fis 2017 vol 3 1 nonfunctional pituitary tumours